Klotho G-395A基因多态性与ESRD患者钙磷代谢紊乱的相关性分析

目的观察终末期肾病(ESRD)患者klotho G-395A基因多态性分布与其合并钙磷代谢紊乱的相关性。 方法选取2015年4月至2016年12月期间就诊于扬州市多个血液净化中心的ESRD患者共137例，体检中心正常体检者80名为对照组；运用FQ-PCR(TaqMan法)对各研究对象进行klotho基因G-395A多态性分型；检测klotho蛋白、成纤维细胞生长因子(FGF23)及钙磷代谢相关生化指标水平，比较不同基因型间各生化指标间的水平。卡方检验、t检验、单因素方差分析、Mann-Whitney U检验及Kruskal-Wallis H检验用于各组生化指标间差异性分析，多因素采用二元logistic回归分析。 结果①ESRD组和健康对照组的基因型分布均符合Hardy-Weinberg平衡(χ²＝0.512, χ²＝0.134; P<0.05)。②ESRD组和对照组基因亚型及基因频率分布差异有统计学意义(χ² ＝11.467, P＝0.003; χ²＝10.130, P＝0.001)，且ESRD组患者A等位基因频率较对照组高。③ESRD组不同的基因型中，血钙、klotho蛋白及FGF23水平差异有统计学意义(P<0.05)，血钙在GA型与AA型间表达水平差异有统计学意义(t＝－2.469，P＝0.015), FGF23、klotho蛋白在GG与AA型(Z＝－4.020, Z＝－5.461; P<0.001)，GA与AA型(Z＝－4.303, Z＝－5.610; P<0.001)之间的表达水平差异均有统计学意义。④二元logistic回归分析示GA＋AA型为ESRD患者钙磷代谢紊乱的独立危险因素。 结论Klotho G-395A基因多态性A等位基因位点可能为ESRD患者的易感基因，并与ESRD患者合并钙磷代谢紊乱有关。

Correlation analysis between klotho G-395A polymorphism and calcium and phosphorus metabolic disorders in ESRD patients

ObjectiveTo explore the correlation between klotho G-395A polymorphism and calcium and phosphorus metabolic disorders in end-stage renal disease (ESRD) patients. MethodsA total of 137 patients with ESRD who were admitted to the Yangzhou Multi-central Blood Purification Center from April 2015 to December 2016 were selected. 80 people with normal physical examination from the physical examination center were enrolled as control. The klotho G-395A polymorphism was analyzed with TaqMan FQ-PCR method. The levels of klotho protein, fibroblast growth factor (FGF23), and calcium and phosphorus metabolism-related biochemical indicators were also measured and compared. Chi-square test, t-test, one-way ANOVA, Mann-Whitney U test, and Kruskal-Wallis H test were used to analyze the differences. The binary logistic regression method was performed for multivariate analysis. Results① The genotypes distributions of the ESRD group and the healthy control group were consistent with the Hardy-Weinberg equilibrium (χ²=0.512, χ² =0.134; P<0.05). ② There were significant differences in gene subtypes and gene frequency distributions between the ESRD group and the control group (χ²=11.467, P=0.003; χ²=10.130, P=0.001), and the A allele frequency was higher in the ESRD group than in the control group. ③ There were significant differences in serum calcium, klotho protein, and FGF23 levels among different genotypes of the ESRD group (P<0.05). There was a statistically significant difference in the level of serum calcium between the GA and the AA types (t=-2.469, P=0.015). There were statistically significant differences in the expression levels of FGF23 and klotho proteins between the GG and the AA types (Z=-4.020, Z=-5.461; P<0.001), as well as between the GA and the AA types (Z=-4.303, Z=- 5.610; P<0.001). ④ Binary logistic regression analysis showed that GA+ AA type was an independent risk factor for calcium and phosphorus metabolism disorders in the ESRD patients. ConclusionThe klotho G-395A polymorphism A allele locus might be a susceptibility gene for the ESRD patients, and was related to the calcium and phosphorus metabolism disorders in the ESRD patients.